A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study

BMC Pulmonary Medicine

Peter D’Andrea²  Tim Overend³  Hungta Chen²  Michelle Henley²  Robert Nutbrown³  Anthony D’Urzo¹  Eric D Bateman⁴  Jutta Beier⁶  Kai-Michael Beeh⁶  Kenneth R Chapman⁵ 

[1] Department of Family and Community Medicine, University of Toronto, Toronto ON, Canada;Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA;Novartis Horsham Research Centre, West Sussex, UK;University of Cape Town, Cape Town, South Africa;Asthma and Airway Centre, University Health Network, Toronto Western Hospital, Rm 7-451 East Wing, 399 Bathurst Street, Toronto, ON, Canada;Insaf Respiratory Research Institute, Wiesbaden, Germany

关键词: Blinding;    Long-acting muscarinic antagonist;    Bronchodilator;    Tiotropium;    Breezhaler;    Glycopyrronium;    COPD;   

Others  :  865452
DOI  :  10.1186/1471-2466-14-4

 received in 2013-07-11, accepted in 2013-12-31,  发布年份 2014

【 摘 要 】

Background

Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) – tiotropium and glycopyrronium. Previous studies have compared glycopyrronium with open-label tiotropium. In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.

Methods

In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily. The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV₁) following 12 weeks of treatment (non-inferiority margin: –50 mL). Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.

Results

657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study. Least squares mean trough FEV₁ for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: –32, 31 mL). Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV₁ at all time points from 0–4 h post-dose versus tiotropium (all p < 0.001). FEV₁ area under the curve from 0–4 h (AUC_0–4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12. Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant). Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035). Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).

Conclusion

In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.

Trial registration

ClinicalTrial.gov, NCT01613326

【 授权许可】

   
2014 Chapman et al.; licensee BioMed Central Ltd.

【 图 表 】

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